Evidence suggests that insulin resistance accompanied by compensatory hyperinsulinemia is a common feature of polycystic ovary syndrome (PCOS), and that hyperinsulinemia is responsible in part for the hyperandrogenism of the disorder. In this project, the hypothesis that hyperinsulinemia plays a pathogenetic role in the hyperandrogenism and anovulation of both lean and obese women with PCOS will be tested. Separate effects of hyperinsulinemia will be tested in three clinical protocols in vivo. Protocol I will examine the effects of hyperinsulinemia on ovarian androgen production (namely P450c17( activity), serum androgens and the serum sex hormone-binding globulin concentration in lean women with PCOS. Protocol II will examine insulin effects on gonadotropin (LH)) secretory dynamics in both obese and lean women with PCOS. The last protocol will examine the effects of insulin-sensitizing agents on spontaneous ovulatory function and clomiphene responsiveness in obese women with PCOS. If these studies confirm an important role of hyperinsulinemia in the pathogenesis of PCOS, then a possible first-line treatment for hyperandrogenism and / or anovulation would be measures aimed at improving insulin sensitivity and reducing serum insulin-- be that diet and weight loss or the use of "insulin-sensitizing" agents.